American Journal of Medical Genetics 42714-715 (1992)
Brief Clinical Report Congenital Absence of the Vas Deferens: Recurrence in a Family Rick A. Martin, Kenneth Lyons Jones, and Earl C. Downey Division of Dysmorphology, Department of Pediatrics, University of California, San Diego
We report on 2 brothers with congenital absence of the vas deferens discovered in childhood during inguinal hernia repairs. The vas is absent unilaterally in one sib and bilaterally in the other. The unusual presentation of inguinal hernias in these children is discussed as well as mechanisms of inheritance and associated risk of renal anomalies.
cated pregnancy. Delivery was spontaneous and vaginal without complications. Birth weight was 2,740 g, length 51 cm, and OFC 33 cm. His 3-year-old brother presented with bilateral indirect inguinal hernias in the first year of life. They were repaired a t 19 months. At the time of his brother’s surgery bilateral absence of the vas deferens was discovered although normal-appearing epididymides were identified. We first evaluated the propositus at age 11months. At that time his weight was 9.2 kg, length 76 cm, and OFC 45.5 cm. No structural abnorKEY WORDS: Wolffian duct, familial, renal malities were noted on physical examination. At 18 defect months he presented to the pediatric surgery clinic with a right indirect inguinal hernia that was repaired shortly thereafter. At surgery a normal epididymis was INTRODUCTION located but no connecting vas deferens could be identiBilateral congenital absence of the vas deferens fied. Because of the bilateral absence of the vas deferens (CAVD) is a malformation usually discovered during a in the patient’s older sib the left groin was also explored. male infertility work-up and accounts for 1-2% of male No hernia was identified and there was a normal-apsterility [Dubin and Amelar, 1971;Hellinga et al., 1971; pearing vas deferens. No direct observation of a connecJequier et al., 1985; Michelson, 1949; Vaze, 19671. The tion between the proximal vas deferens with the epiprevalence of unilateral CAVD is difficult to ascertain didymis on the left was attempted because of injury risk since fertility is usually unimpaired but has been esti- but this connection was easily palpable preoperatively. mated at one to 8 per 1,000 males from series of vasecBoth sibs have had normal sweat chloride studies and tomies [Deane and May, 1982; Emery et al., 1974; Klap- the older brother has normal chromosomes. Both boys proth and Young, 1973; Schmidt, 19661. CAVD have also had normal renal ultrasound results. The generally occurs sporadically, but 7 families have been father of these children was found to have palpable vas reported with familial recurrence of documented bilat- deferens and epididymides by urological examination. eral CAVD [Budde et al., 1984; Czeizel, 1985; Gilgenkrantz et al., 1990; Kleczkowska et al., 1989; SchelDISCUSSION len and van Straaten, 19801. We report the first family in which both unilateral The boys presented here represent the first children and bilateral CAVD occurred in a sibship. Since fertility described with unilateral and bilateral CAVD and bring is unaffected in unilateral CAVD, this observation has to 8 the number of documented familial cases. Thus potential implications with respect to inheritance and familial CAVD may be more prevalent than previously suggests that familial CAVD may be more common than reported since fertility is unaffected in unilateral previously documented. CAVD. In fact, it is unlikely that the unilateral CAVD in this case would ever have been discovered except for CLINICAL REPORT repair of the concordant inguinal hernia. The propositus, now 2 years old, was born at 40 weeks of The concordance of inguinal hernias with the side of gestation to a 28-year-oldG2P2 mother after an uncompli- the missing vas in these 2 boys is unusual. Lukash et al. [19751 reviewed 800 inguinal herniorrhaphies over a 5-year period and found only 4 cases (0.5%)of CAVD in Received for publication May 13,1991; revision received July 10, otherwise normal boys. Conversely, inguinal hernias have not been described frequently with either sporadic 1991. Address reprint requests to Kenneth Lyons Jones, M.D., Univer- or familial cases of CAVD. In fact, we have located only sity of California San Diego Medical Center, Department of Pedi- one other case [Hershman et al., 19901 in a child with unilateral CAVD and a renal anomaly. atrics, 225 Dickinson St., H814B,San Diego, CA 92103.
0 1992 Wiley-Liss, Inc.
Vas Deferens
While neither of the boys reported here nor any of the other familial cases of CAVD have evidence of a renal defect, the association between sporadic CAVD and renal anomalies is well documented [Buresh and Caterine, 1979; Deane and May, 1982; Donohue and Fauver, 1989;Emergy et al., 1974;Rubin, 19751.In fact, the study by Donohue and Fauver [19891shows that 91% of unilateral CAVD cases have a renal malformation, most commonly ipsilateral renal agenesis. Many patients in their study presented with urologic complaints, which certainly biases this figure, yet the high frequency of this association is still impressive. In addition, Rubin 119751 reported that 22% of patients with bilateral CAVD also had a significant renal defect. Such an association is not surprising since a common early defect in the fetal mesonephros could cause malformations in both the Wolffian duct and the kidney. However, renal defects among the familial cases of CAVD are absent in those individuals so evaluated and strongly suggest a different mechanism. The familial form of CAVD may represent a specificdefect of later Wolffian duct differentiation rather than an early mesonephric defect. Autosomal recessive inheritance has been suggested for familial CAVD in prior reports. However, a family in which the propositus and his maternal uncle both had bilateral CAVD casts serious doubt on that possibility [Kleczkowska et al., 19891. A far more likely possibility is X-linked recessive or autosomal dominant sex-limited inheritance. The key to differentiating these 2 mechanisms of inheritance in a defect with sex-limited expression ultimately lies in whether affected males have affected sons. Obviously, vertical transmission cannot be ascertained in males with bilateral CAVD. However, the family presented here shows that unilateral CAVD occurs as part of this familial pattern, making father-toson transmission possible if it is an autosomal dominant trait. For this reason all fathers of affected males should be examined for the presence of unilateral CAVD. Theoretically, females carrying an autosomal dominant CAVD gene should lack the normal remnant of Wolffian duct regression (Gartner duct) while these remnants should be present in females carrying an X-linked recessive gene. Unfortunately, the Gartner duct is a clinically undetectable structure and thus is difficult to use to differentiate between these 2 modes of inheritance. More large family evaluations will be necessary to delineate the inheritance pattern in these familial cases of CAVD. Finally, CAVD is likely a heterogeneous condition. Besides sporadic and familial occurrences it is also a frequent finding in individuals with cystic fibrosis [Denning et al., 1968; Kaplan et al., 19681 and accounts for the usual male infertility found in that condition.Therefore, any child found with CAVD should be evaluated for cystic fibrosis. In addition, children diagnosed with CAVD should be studied cytogenetically because at least 2 cases of Klinefelter syndrome have been reported
715
in association with CAVD [Fuse et al., 1990;Leiba et al., 19691. ACKNOWLEDGMENTS This work was supported in part by NIH training grant #DK07318.
REFERENCES Budde WJAM, Vejaal M, Hamerlynck VTH, Bobrow M (1984):Familial occurrence of azoospermia and extreme oligospermia. Clin Genet 26:555-562. Buresh WS, Caterine J M (1979):Renal agenesis associated with a congenitally absent vas deferens. J Iowa Med Soc 69:97-98. Czeizel A (1985):Congenital aplasia ofthe vasa deferentia of autosomal recessive inheritance in two unrelated sib-pairs. Hum Genet 70:288. Deane AM, May RE (1982):Absent vas deferens in association with renal abnormalities. Br J Urol 54298-299. Denning CR, Sommers SC, Quigley HJ (1968):Infertility in male patients with cystic fibrosis. Pediatrics 41:7-17. Donohue RE, Fauver H (1989):Unilateral absence ofthe vasdeferens: a useful clinical sign. JAMA 261:1180-1182. Dubin L, Amelar RD (1971):Etiologic factors in 1294 consecutive cases of male infertility. Fertil Steril 22:469-474. Emery CB, Goldstein AMB, Morrow J W (1974):Congenital absence of vas deferens with ipsilateral urinary anomalies. Urology 4201203. Fuse H, Shiseki Y,Shimazaki J, Katayama T (1990):A case of Klinefelter’s syndrome with bilateral absence of the vas deferens. Urol Int 45:181-182. Gilgenkrantz S, Guillemin P, Kimmel B (1990):On the familial occurrence of congenital bilateral absence of vas deferens. Clin Genet 37:159. Hellinga G, Ultee WA, Rubvard R (1971):Bilateral and unilateral congenital anomalies of the Wolfiian ducts. Andrologie 3:81-84. Hershman MJ, Dawson PM, Leung AWL, Singh MP (1990):Cystic dysplasia in ectopic kidney associated with absent vas deferens and congenital inguinal hernia. Urology 35:331-333. Jequier AM, Ansell ID, Bullimore NJ (1985):Congenital absence of the vasa deferentia presenting with infertility. J Androl (315-19. Kaplan E, Schwachman H, Perlmutter AD, Rule A, Khaw KT, Holsclaw DS (1968):Reproductive failure in males with cystic fibrosis. N Engl J Med 279:65-69. Klapproth HJ, Young ID (1973):Vasectomy, vas ligation and vas occlusion. Urology 1:292-300. Kleczkowska A, Fryns JP, Steeno 0, van den Berghe H (1989):On the familial occurrence of congenital bilateral absence of vas deferens. Clin Genet 35:268-271. Leiba S, Ber A, Joshua H, Lazebnik J , Ben-Basset M (1969):A case of XY/XXY mosaicism and bilateral absence ofthe vas deferens. Acta Endocrinol (Stockh) 62:498-504. Lukash F, Zwiren GT, Andrews HG (1975):Significance of absent vas deferens at hernia repair in infants and children. J Pediatr Surg 10:765-769. Michelson L (1949):Congenital anomalies of the ductus deferens and epididymis. J Urol 61:384-390. Rubin S (1975):Congenital absence of the vas deferens. Scand J Urol Nephrol 9:94-99. Schellen TMCM, van Straaten A (1980):Autosomal recessive hereditary congenital aplasia ofthe vasa deferentia in four siblings. Fertil Steril 34:401-404. Schmidt SS (1966):Techniques and complications of elective vasectomy. Fertil Steril 17:467-482. Vaze ML (1967):Obstructive azoospermia. Indian J Surg 29660-662.
Brief Clinical Report Congenital Absence of the Vas Deferens: Recurrence in a Family Rick A. Martin, Kenneth Lyons Jones, and Earl C. Downey Division of Dysmorphology, Department of Pediatrics, University of California, San Diego
We report on 2 brothers with congenital absence of the vas deferens discovered in childhood during inguinal hernia repairs. The vas is absent unilaterally in one sib and bilaterally in the other. The unusual presentation of inguinal hernias in these children is discussed as well as mechanisms of inheritance and associated risk of renal anomalies.
cated pregnancy. Delivery was spontaneous and vaginal without complications. Birth weight was 2,740 g, length 51 cm, and OFC 33 cm. His 3-year-old brother presented with bilateral indirect inguinal hernias in the first year of life. They were repaired a t 19 months. At the time of his brother’s surgery bilateral absence of the vas deferens was discovered although normal-appearing epididymides were identified. We first evaluated the propositus at age 11months. At that time his weight was 9.2 kg, length 76 cm, and OFC 45.5 cm. No structural abnorKEY WORDS: Wolffian duct, familial, renal malities were noted on physical examination. At 18 defect months he presented to the pediatric surgery clinic with a right indirect inguinal hernia that was repaired shortly thereafter. At surgery a normal epididymis was INTRODUCTION located but no connecting vas deferens could be identiBilateral congenital absence of the vas deferens fied. Because of the bilateral absence of the vas deferens (CAVD) is a malformation usually discovered during a in the patient’s older sib the left groin was also explored. male infertility work-up and accounts for 1-2% of male No hernia was identified and there was a normal-apsterility [Dubin and Amelar, 1971;Hellinga et al., 1971; pearing vas deferens. No direct observation of a connecJequier et al., 1985; Michelson, 1949; Vaze, 19671. The tion between the proximal vas deferens with the epiprevalence of unilateral CAVD is difficult to ascertain didymis on the left was attempted because of injury risk since fertility is usually unimpaired but has been esti- but this connection was easily palpable preoperatively. mated at one to 8 per 1,000 males from series of vasecBoth sibs have had normal sweat chloride studies and tomies [Deane and May, 1982; Emery et al., 1974; Klap- the older brother has normal chromosomes. Both boys proth and Young, 1973; Schmidt, 19661. CAVD have also had normal renal ultrasound results. The generally occurs sporadically, but 7 families have been father of these children was found to have palpable vas reported with familial recurrence of documented bilat- deferens and epididymides by urological examination. eral CAVD [Budde et al., 1984; Czeizel, 1985; Gilgenkrantz et al., 1990; Kleczkowska et al., 1989; SchelDISCUSSION len and van Straaten, 19801. We report the first family in which both unilateral The boys presented here represent the first children and bilateral CAVD occurred in a sibship. Since fertility described with unilateral and bilateral CAVD and bring is unaffected in unilateral CAVD, this observation has to 8 the number of documented familial cases. Thus potential implications with respect to inheritance and familial CAVD may be more prevalent than previously suggests that familial CAVD may be more common than reported since fertility is unaffected in unilateral previously documented. CAVD. In fact, it is unlikely that the unilateral CAVD in this case would ever have been discovered except for CLINICAL REPORT repair of the concordant inguinal hernia. The propositus, now 2 years old, was born at 40 weeks of The concordance of inguinal hernias with the side of gestation to a 28-year-oldG2P2 mother after an uncompli- the missing vas in these 2 boys is unusual. Lukash et al. [19751 reviewed 800 inguinal herniorrhaphies over a 5-year period and found only 4 cases (0.5%)of CAVD in Received for publication May 13,1991; revision received July 10, otherwise normal boys. Conversely, inguinal hernias have not been described frequently with either sporadic 1991. Address reprint requests to Kenneth Lyons Jones, M.D., Univer- or familial cases of CAVD. In fact, we have located only sity of California San Diego Medical Center, Department of Pedi- one other case [Hershman et al., 19901 in a child with unilateral CAVD and a renal anomaly. atrics, 225 Dickinson St., H814B,San Diego, CA 92103.
0 1992 Wiley-Liss, Inc.
Vas Deferens
While neither of the boys reported here nor any of the other familial cases of CAVD have evidence of a renal defect, the association between sporadic CAVD and renal anomalies is well documented [Buresh and Caterine, 1979; Deane and May, 1982; Donohue and Fauver, 1989;Emergy et al., 1974;Rubin, 19751.In fact, the study by Donohue and Fauver [19891shows that 91% of unilateral CAVD cases have a renal malformation, most commonly ipsilateral renal agenesis. Many patients in their study presented with urologic complaints, which certainly biases this figure, yet the high frequency of this association is still impressive. In addition, Rubin 119751 reported that 22% of patients with bilateral CAVD also had a significant renal defect. Such an association is not surprising since a common early defect in the fetal mesonephros could cause malformations in both the Wolffian duct and the kidney. However, renal defects among the familial cases of CAVD are absent in those individuals so evaluated and strongly suggest a different mechanism. The familial form of CAVD may represent a specificdefect of later Wolffian duct differentiation rather than an early mesonephric defect. Autosomal recessive inheritance has been suggested for familial CAVD in prior reports. However, a family in which the propositus and his maternal uncle both had bilateral CAVD casts serious doubt on that possibility [Kleczkowska et al., 19891. A far more likely possibility is X-linked recessive or autosomal dominant sex-limited inheritance. The key to differentiating these 2 mechanisms of inheritance in a defect with sex-limited expression ultimately lies in whether affected males have affected sons. Obviously, vertical transmission cannot be ascertained in males with bilateral CAVD. However, the family presented here shows that unilateral CAVD occurs as part of this familial pattern, making father-toson transmission possible if it is an autosomal dominant trait. For this reason all fathers of affected males should be examined for the presence of unilateral CAVD. Theoretically, females carrying an autosomal dominant CAVD gene should lack the normal remnant of Wolffian duct regression (Gartner duct) while these remnants should be present in females carrying an X-linked recessive gene. Unfortunately, the Gartner duct is a clinically undetectable structure and thus is difficult to use to differentiate between these 2 modes of inheritance. More large family evaluations will be necessary to delineate the inheritance pattern in these familial cases of CAVD. Finally, CAVD is likely a heterogeneous condition. Besides sporadic and familial occurrences it is also a frequent finding in individuals with cystic fibrosis [Denning et al., 1968; Kaplan et al., 19681 and accounts for the usual male infertility found in that condition.Therefore, any child found with CAVD should be evaluated for cystic fibrosis. In addition, children diagnosed with CAVD should be studied cytogenetically because at least 2 cases of Klinefelter syndrome have been reported
715
in association with CAVD [Fuse et al., 1990;Leiba et al., 19691. ACKNOWLEDGMENTS This work was supported in part by NIH training grant #DK07318.
REFERENCES Budde WJAM, Vejaal M, Hamerlynck VTH, Bobrow M (1984):Familial occurrence of azoospermia and extreme oligospermia. Clin Genet 26:555-562. Buresh WS, Caterine J M (1979):Renal agenesis associated with a congenitally absent vas deferens. J Iowa Med Soc 69:97-98. Czeizel A (1985):Congenital aplasia ofthe vasa deferentia of autosomal recessive inheritance in two unrelated sib-pairs. Hum Genet 70:288. Deane AM, May RE (1982):Absent vas deferens in association with renal abnormalities. Br J Urol 54298-299. Denning CR, Sommers SC, Quigley HJ (1968):Infertility in male patients with cystic fibrosis. Pediatrics 41:7-17. Donohue RE, Fauver H (1989):Unilateral absence ofthe vasdeferens: a useful clinical sign. JAMA 261:1180-1182. Dubin L, Amelar RD (1971):Etiologic factors in 1294 consecutive cases of male infertility. Fertil Steril 22:469-474. Emery CB, Goldstein AMB, Morrow J W (1974):Congenital absence of vas deferens with ipsilateral urinary anomalies. Urology 4201203. Fuse H, Shiseki Y,Shimazaki J, Katayama T (1990):A case of Klinefelter’s syndrome with bilateral absence of the vas deferens. Urol Int 45:181-182. Gilgenkrantz S, Guillemin P, Kimmel B (1990):On the familial occurrence of congenital bilateral absence of vas deferens. Clin Genet 37:159. Hellinga G, Ultee WA, Rubvard R (1971):Bilateral and unilateral congenital anomalies of the Wolfiian ducts. Andrologie 3:81-84. Hershman MJ, Dawson PM, Leung AWL, Singh MP (1990):Cystic dysplasia in ectopic kidney associated with absent vas deferens and congenital inguinal hernia. Urology 35:331-333. Jequier AM, Ansell ID, Bullimore NJ (1985):Congenital absence of the vasa deferentia presenting with infertility. J Androl (315-19. Kaplan E, Schwachman H, Perlmutter AD, Rule A, Khaw KT, Holsclaw DS (1968):Reproductive failure in males with cystic fibrosis. N Engl J Med 279:65-69. Klapproth HJ, Young ID (1973):Vasectomy, vas ligation and vas occlusion. Urology 1:292-300. Kleczkowska A, Fryns JP, Steeno 0, van den Berghe H (1989):On the familial occurrence of congenital bilateral absence of vas deferens. Clin Genet 35:268-271. Leiba S, Ber A, Joshua H, Lazebnik J , Ben-Basset M (1969):A case of XY/XXY mosaicism and bilateral absence ofthe vas deferens. Acta Endocrinol (Stockh) 62:498-504. Lukash F, Zwiren GT, Andrews HG (1975):Significance of absent vas deferens at hernia repair in infants and children. J Pediatr Surg 10:765-769. Michelson L (1949):Congenital anomalies of the ductus deferens and epididymis. J Urol 61:384-390. Rubin S (1975):Congenital absence of the vas deferens. Scand J Urol Nephrol 9:94-99. Schellen TMCM, van Straaten A (1980):Autosomal recessive hereditary congenital aplasia ofthe vasa deferentia in four siblings. Fertil Steril 34:401-404. Schmidt SS (1966):Techniques and complications of elective vasectomy. Fertil Steril 17:467-482. Vaze ML (1967):Obstructive azoospermia. Indian J Surg 29660-662.
